This invention relates to a novel polypeptide growth factor and, more particularly, to a prostate-derived growth factor or mitogen.
In recent years a considerable number of growth factors derived from various animal cells have been isolated and characterized. Illustrative of these growth factors are nerve growth factor (NGF) which has been purified from several different cell sources, insulin-like growth factors (IGF-I and IGF-II), epidermal growth factor (EGF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), endothelial cell growth factor (ECGF), somatomedins and transforming growth factors (TGF) derived from various tumors and virally transformed cells. For background information on these growth factors see, for example, the recent brief review article by Kris et al., Biotechnology, February 1985, pp. 135-140; and the comprehensive review in Hormonal Proteins and peptides, Ed. by Choh Hao Li, Vol. 12, "Growth Factors," Academic Press, 1984.
These growth factors, many of which are polypeptide hormone-like agents in structure, function to regulate the proliferation, differentiation and survival of animal cells. The isolation and characterization of these growth factors is of major importance for understanding the regulation of normal tissue specific DNA synthesis and cell division, as well as for understanding abnormal mechanisms of cell growth such as observed in atherosclerosis and in neoplasia. Growth factor activity in prostate glands may be especially important to characterize because benign prostatic hypertrophy and prostate cancer are common tumors in males and because prostatic cancer metastatic to bone is nearly unique in inducing osteoblasts to form new bone locally. Thus, trophic factors that are secreted by prostatic tissue may be important not only in the normal growth and differentiation of prostatic tissue but also as mediators of abnormal prostatic growth.
The concept of a trophic factor released by metastatic prostatic carcinoma cells in bone has been suggested heretofore. See Franks, J. Path. Bact. 72, 603-611 (1956); Cook et al, J. Urol . 99, 87-96 (1968); Galasko, J. Bone Joint Surg. 57B, 353-359 (1973); Warren et al, Arch. Pathol. 22, 139-160 (1936); and Rosai, in Pathology, eds. Anderson and Kissane, C. V. Mosby Co., St. Louis, 7th. ed., 1977, pp. 1978-2014. Growth factor activity in extracts of prostatic tissue have been previously demonstrated but not purified or characterized. See Lawson et al, in The Prostatic Cell: Structure and Function, Part A, eds. Murphy et al, Alan R. Liss, Inc., N.Y. 1981, pp. 325-336; Story et al, J. Urol. 130, 175-179 (1983 ); and Jacobs et al Urol. 16, 488-491 (1980) A mRNA fraction in human prostatic cancer cells coding for a novel osteoblast-stimulating factor having a molecular weight of .about.20,000 has recently been identified and associated with this activity by Simpson et al, Endocrinology 117, 1615-1620 (1985) . Tackett et al, J. Urology 133, 45-48 (1985), disclose the presence of a mitogenic factor in expressed prostatic secretions in humans of about 30,000 daltons. However, no purification or characterization of the mitogenic factor is given.
In copending application Ser. No. 06/815,685, filed Jan. 2, 1986, a novel 25 kDa prostate-derived growth factor and a process for its preparation from rat prostate cells are disclosed. This growth factor, also designated as PrGF or PrDGF, was demonstrated to differ from previously described growth factors. The disclosure of said application was subsequently essentially published by Maehama et al, Proc. Natl. Acad. Sci. USA 83, 8162-8166 (1986).